The role of microfibril-associated glycoprotein-1 in experimental liver fibrosis [bulk RNA-seq]

Microfibril-associated glycoprotein-1 (MAGP-1), a critical component of extracellular matrix (ECM) microfibrils, plays a pivotal role in liver fibrosis, although its precise function in this process remains elusive. Our research underscores that MAGP-1 (Mfap2) is predominantly expressed in activated hepatic stellate cells (HSCs) and exhibits heightened levels in advanced liver fibrosis. Deletion of MAGP-1 showcased limited impact on overall collagen deposition following CCl4 stimulation. However, it notably heightened intrahepatic inflammatory infiltration within lobular regions, hastened ECM stabilization through the upregulation of insoluble matrisome constituents within the ECM, and triggered focal adhesion (FA) signaling in HSCs, hindering the regression of liver fibrosis upon cessation of CCl4 treatment. Bulk RNA-seq analysis was conducted on frozen livers from CCl4-treated Mfap2+/+ and Mfap2-/- mice (8W, n=4 for each group of mice) and from Mfap2+/+ and Mfap2-/- mice undergoing fibrosis reversal (4W, n=4 for each group of mice) . Additionally, scRNA-seq was performed on liver NPCs isolated from CCl4-injected Mfap2+/+ and Mfap2-/- mice (8 weeks).